The goal is to provide a better understanding of tryptophan and lysine-hydroxylysine catabolism and of regulatory interactions in these pathways that may be important in normal and pathological functions in mammals. Our previous work has shown that kynurenine aminotransferase, alpha-aminoadipate aminotransferase and halogenated tyrosine aminotransferase are identical, thus demonstrating that the known properties of kynurenine aminotransferase are applicable to the other two activities. We have purified the enzyme to near homogeneity from rat kidney supernatant and are purifying it by similar methodology from rat kidney and liver mitochondria. We propose to continue kinetic and structural comparisons of this purified enzyme with purified aspartate aminotransferase as a means of clarifying transamination mechanisms. Based on our new knowledge concerning the properties of alpha-aminoadipate aminotransferase we have proposed experiments to delineate its function in lysine-hydroxylysine catabolism and in interactions of that pathways with the tryptophan pathway. Based on preliminary evidence for abnormalities of lysine metabolism in patients with Reye's syndrome, we propose to analyze sera and urine of additional patients to help clarify the metabolic abnormalities of the disease. Experiments with an animal model of the disease are proposed as a means of probing the basic causes of the abnormalities. We have discovered a specific requirement for Ca ions in controlling the rate of kynurenine (alpha-aminoadipate, halogenated tyrosine) amino-transferase of isolated kidney mitochondria. We propose further experiments to determine the mechanism of the action and to explain its significance in metabolic regulation.